The molecular basis of differential host responses to avian influenza viruses in avian species with differing susceptibility.

The molecular basis of differential host responses to avian influenza viruses in avian species with differing susceptibility.
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DOI:
10.3389/fcimb.2023.1067993
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发表时间:
2023
影响因子:
5.7
通讯作者:
--
中科院分区:
医学2区
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H5N1 等高致病性禽流感 (HPAI) 病毒继续对畜牧业、野生动物和公众健康构成严重威胁。控制和减轻家禽中的这种疾病需要更好地了解是什么导致某些物种高度易感(例如火鸡和鸡),而另一些物种则高度耐药(例如鸽子和鹅)。对 H5N1 的易感性因物种和毒株而异;例如,对大多数 H5N1 病毒株具有耐受性的物种,如乌鸦和鸭子,近年来对新出现的病毒株表现出很高的死亡率。因此,在本研究中,我们旨在检查和比较这 6 个物种对低致病性禽流感 (H9N2) 和具有不同毒力的两种 H5N1 毒株(进化枝 2.2 和进化枝 2.3.2.1)的反应,以确定易感和耐受物种如何应对 HPAI 挑战。鸟类在感染试验中受到挑战,并在感染后的三个时间点收集样本(脑、回肠和肺)。使用比较方法检查鸟类的转录组反应,揭示了几个重要的发现。我们发现易感鸟类的大脑中病毒载量高且神经炎症反应强烈,这可能解释了 H5N1 感染后表现出的神经系统症状和高死亡率。我们发现肺和回肠中与神经功能相关的基因存在差异调节,在抗性物种中差异调节更强。这对于病毒向中枢神经系统(CNS)的传播具有有趣的意义,也可能表明粘膜表面的神经免疫参与。此外,我们发现鸭子和乌鸦在感染更致命的 H5N1 毒株后免疫反应时间延迟,这可能是该毒株导致这些物种死亡率较高的原因。最后,我们确定了在易感性/耐药性中具有潜在作用的候选基因,这为未来的研究提供了极好的目标。这项研究有助于阐明禽类对 H5N1 流感易感性的潜在反应,这对于制定未来控制家禽高致病性禽流感的可持续策略至关重要。
Highly pathogenic avian influenza (HPAI) viruses, such as H5N1, continue to pose a serious threat to animal agriculture, wildlife and to public health. Controlling and mitigating this disease in domestic birds requires a better understanding of what makes some species highly susceptible (such as turkey and chicken) while others are highly resistant (such as pigeon and goose). Susceptibility to H5N1 varies both with species and strain; for example, species that are tolerant of most H5N1 strains, such as crows and ducks, have shown high mortality to emerging strains in recent years. Therefore, in this study we aimed to examine and compare the response of these six species, to low pathogenic avian influenza (H9N2) and two strains of H5N1 with differing virulence (clade 2.2 and clade 2.3.2.1) to determine how susceptible and tolerant species respond to HPAI challenge. Birds were challenged in infection trials and samples (brain, ileum and lung) were collected at three time points post infection. The transcriptomic response of birds was examined using a comparative approach, revealing several important discoveries. We found that susceptible birds had high viral loads and strong neuro-inflammatory response in the brain, which may explain the neurological symptoms and high mortality rates exhibited following H5N1 infection. We discovered differential regulation of genes associated with nerve function in the lung and ileum, with stronger differential regulation in resistant species. This has intriguing implications for the transmission of the virus to the central nervous system (CNS) and may also indicate neuro-immune involvement at the mucosal surfaces. Additionally, we identified delayed timing of the immune response in ducks and crows following infection with the more deadly H5N1 strain, which may account for the higher mortality in these species caused by this strain. Lastly, we identified candidate genes with potential roles in susceptibility/resistance which provide excellent targets for future research. This study has helped elucidate the responses underlying susceptibility to H5N1 influenza in avian species, which will be critical in developing sustainable strategies for future control of HPAI in domestic poultry.
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